Mount Kazbek in Georgia's Caucasus Mountains, with Gergeti Trinity Church to the right.

Mount Kazbek in Georgia's Caucasus Mountains, with Gergeti Trinity Church to the right.

CREDIT: By Philipp Weigell (Own work) [CC BY 3.0], via Wikimedia Commons

Overcoming Regulatory Obstacles

When a house is on fire, you don't wait for scientific proof; you grab the first hose and you start putting out the fire

Dr. Don Francis, as portrayed by actor Matthew Modine in the HBO drama And the Band Played On; reacting to what he perceived as excessive bureaucratic foot-dragging among U.S. health officials in addressing the exploding HIV/AIDS pandemic in the early 1980s.

Outlining the Challenge

And the Band Played On; a 1993 HBO drama drawn from journalist Randy Shilts' 1987 book of the same name, depicts a U.S. response to the emergence of HIV/AIDS during the early 1980s which was hobbled by scientific rivalry and government inaction. The film goes so far as to suggest that U.S Centers for Disease Control and Prevention (CDC) officials continued to insist upon specific scientific "proof" regarding certain causation factors after the nature of the growing pandemic had become clear enough to warrant decisive action.

ABTI asserts no opinion regarding the accuracy of such claims; yet, the World Health Organization's 2014 report that the emergence of antibiotic-resistant "superbugs" threatens to become a worse global health crisis than the HIV/AIDS pandemic suggests some unsettling parallels. Specifically, while a global consensus has emerged regarding the character, scope, and potential severity of the antibiotic resistance crisis, the U.S. Food and Drug Administration (FDA) does not seem to have assumed any discernible sense of urgency. According to statistics reported in Prevention magazine and elsewhere, "[m]ore than 2 million Americans each year get sick from antibiotic-resistant bacteria, which find their victims both in the hospital and in the everyday world. At least 23,000 die annually from those infections."1 Yet, while "experts abroad and in the US" agree that "phages are one of the most promising solutions to our growing problem of resistant bacteria,"2, the FDA remains hidebound in a regulatory scheme calibrated to an antibiotic paradigm.

A Round Peg in a Square Hole: Phages and the FDA

As set forth in more detail in this site's section on Phage Therapy Safety, the FDA has officially certified the safety of phage therapy on multiple occasions. The FDA has even approved the manufacture and sale of phage therapy products designed to enhance food safety. Nevertheless, "[o]wing to a regulatory technicality, [food product] manufacturers can use phages to keep ready-to-eat foods like deli meat and coleslaw safe from bacterial contamination, but doctors can't prescribe them to treat a bad case of strep. The difference, according to the FDA, is the application. Spraying a phage on lunch meat makes it a food additive. Give to someone with an infection, and it becomes a drug."1

Even under the FDA's more stringent drug testing protocols, however, a phage therapy preparation has performed well in both "Phase I" safety testing and "Phase II" efficacy (or effectiveness) trials. "[I]n 2009, a double-blind Phase II clinical study showed phages to be safe and effective at treating chronic drug-resistant ear infections."2 Nevertheless, "the FDA has essentially grafted its traditional antibiotic regulatory protocols onto phage therapy, meaning that all components of a phage cocktail must go through individual clinical trials and that the composition of these cocktails cannot be altered without re-approval."3 In other words, a phage therapy vendor must shepherd its product back through a new multi-million, multi-year testing process each and every time it introduces a new phage into its product.

Phages Are Not Antibiotics - And That's Their Best Trait

Effectively, this requirement strips phage therapy products of their greatest attribute; placing them in the same straightjacket as antibiotics. Antibiotics are becoming useless against deadly "superbugs" because these static chemical compounds have not kept pace with bacterial mutations. Phages evolve to counter these bacterial mutations. Yet, so-called "Western scientific standards" regard this trait as an unacceptable risk - as if the antibiotic paradigm and the major health crisis it created stand as a model to emulate. Respectfully stated, the FDA and other Western regulatory agencies which follow the same approach owe the populations they serve an explanation.

Phage therapy preparations normally consist of a phage "cocktail" - or a mixture of multiple phages - which a) enables the phage therapy preparation to work against a broader spectrum of bacterial pathogens and b) reduces the ability of bacteria to develop resistance against phages. In the latter case, "'using multiple phages targeting the same [bacterial] pathogen in a cocktail provides a built-in contingency against the development of phage resistance in bacteria.'"1 In other words, as bacterial pathogens evolve to foil specific phage predators, other phages will still be available to kill that bacteria; leading to a more thorough eradication of that particular bacterial pathogen (and ensuring that no "strong" bacteria survive to develop a more generalized resistance to phages)

Due the fact that individual bacterial pathogens might ultimately become resistant to all the phages contained in a particular phage cocktail, however, the necessity periodically arises to introduce new phages into the cocktail. This addition or substitution ensures that "when [bacterial] mutants emerge, new phages with full potency can replace those that no longer work."2 In contrast to antibiotics, locating and extracting a "new" phage for this purpose can be "inexpensive and quick," because "unlike antibiotics, phages are dynamic and can evolve alongside bacteria in a mutually escalating arms race." 3

A Plea for Common Sense

ABTI respectfully submits that the most troubling aspect regarding the FDA's current protocol - aside from the fact that it repeats the tragic mistakes of the antibiotic era - is that it bears little logical relationship to any effort to assure the safety and efficacy of phage therapy products. As Professor Eric C. Keen of the University of Miami has pointed out, "rather than regulate phage cocktails as it does drug cocktails, the FDA could instead regulate phage cocktails in a manner analogous to [the] influenza vaccine. Each year, [the influenza vaccine], a live-virus vaccine comprising a cocktail of three or four . . . strains, is reformulated to most effectively counter circulating flu strains."1

The FDA - and the Western scientific community, for that matter - should also accord the proper dignity and respect to the work of Georgian scientists, which occurred against a backdrop of war, dictatorship, and excruciating poverty. The hard work of these talented men and women over the course of nine decades might not meet "Western standards" of scientific and medical inquiry, but there is no question that the results obtained - in terms of lives saved and an overall healthier standard of living - comport with Western values. Indeed, one could reasonably suggest that the risks which Georgians assumed in perfecting phage therapy constitutes their gift to humanity; one which stands to rescue the Western world from the folly of its over- dependence on antibiotics. Moreover, one must distinguish between the shortcomings of the Soviet system and the achievements of the people who lived under that system. After all, does it stretch the imagination too far to suggest that the same scientific community which beat the West to space could also develop a better solution for defeating bacterial disease?

Prevention magazine notes as follows: "[s]o far, the Sisyphean American solution to [the antibiotic resistance] crisis has been to create more antibiotics, which inevitably lose their potency as the bacteria they're meant to kill mutate and multiply. Even more surreal, a therapy that's been working for a century in a few poor countries on the other side of the world could save many of the thousands of us who die annually in this quiet crisis . . . Drug resistance poses few problems in Georgia, a nation of nearly 5 million, where phage therapy is standard protocol."2

Although Professor Keen agrees with many of his scientist colleagues that "additional research will be needed" to achieve the "promising future" which he predicts "for phage therapy in Western medicine," he acknowledges that "[w]hile it is true that many phage therapy studies did not follow Western protocols, the overall body of evidence suggesting phage therapy’s efficacy, when used appropriately, is significant." 3

Regrettably, however, a significant number of Western scientists - and even some vocal advocates for phage therapy among them - appear to have accepted the unacceptable status quo. For example, a prominent microbiologist who seems devoted to phage therapy states that "'people need to understand that bacteriophage products have to be tested, the production methods have to be standardized, and they must satisfy the FDA. That isn't cheap, easy, or quick.'"4 Another Western scientist who appears to recognize the urgency of the antibiotic resistance crisis nevertheless states that "the realistic goal in the US . . . should be not to import the artful Eastern European phage therapy but, rather, to incorporate phages into existing treatment methods."5

Why?

As Prevention magazine asks, "[w]hy are US doctors and pharmaceutical companies in standby mode and phages still unused while more people die every year?"6

Why not advocate for common sense changes in the FDA's approach, so that the seriously ill people who could benefit from phage therapy can get the relief they desperately need?

Through this site and elsewhere, ABTI intends to serve as a vocal advocate for reform. If you agree with our position, we urge you to spread this page through social media, using the buttons below.